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John P.H. Wilding, DM; Vincent Woo, MD; Norman G. Soler, MD, PhD; Andrea Pahor, MD; Jennifer Sugg, MS; Katja Rohwedder, MD; Shamik Parikh, MD, for the Dapagliflozin 006 Study Group

Persons with type 2 diabetes may have inadequate glycemic control despite high insulin doses, and increasing insulin doses can cause adverse effects. Dapagliflozin inhibits renal absorption of glucose, and clinical trials have shown that it improves glycemic control alone or with metformin. In this 24-week randomized trial, adding dapagliflozin to insulin therapy for inadequately controlled type 2 diabetes improved hemoglobin A1c and weight loss compared with placebo. However, this study could not evaluate long-term effectiveness and safety concerns that have hindered approval of this drug by the U.S. Food and Drug Administration.

Topics: diabetes mellitus, type 2, insulin, dapagliflozin, hemoglobin a
  
Judith A. Long, MD; Erica C. Jahnle, BA; Diane M. Richardson, PhD; George Loewenstein, PhD; and Kevin G. Volpp, MD, PhD

Clinic-based care management interventions have been shown to help patients with diabetes improve glucose control but are expensive. This randomized, controlled trial compared peer mentoring, a modest financial incentive, or usual care in African American veterans, mostly men, with poor diabetes control. Hemoglobin A1c levels decreased more in the peer mentoring group than in the usual care and financial incentive groups. A peer mentorship model could be a scalable approach to improving control in this population and reducing disparities in diabetic outcomes.

Topics: hemoglobin a, veterans, glucose control, incentives, african american, financial incentives, diabetes mellitus, ...
  
J. Christopher Gallagher, MD; Adarsh Sai, MBBS; Thomas Templin II, MD; and Lynette Smith, MS

Vitamin D supplementation is widely recommended to patients, but the optimal dose is debated. This trial randomly assigned postmenopausal white women with vitamin D insufficiency to receive either placebo or increasing doses of vitamin D3, as well as calcium supplements. An 800-IU/d dosage of vitamin D3 achieved a serum 25-hydroxyvitamin D level greater than 50 nmol/L in 97.5% of women. A model predicted the same response with 600 IU/d, although this dosage was not studied.

Topics: cholecalciferol, vitamin d, calcium, postmenopause
  
Maryam Kavousi, MD, MSc; Suzette Elias-Smale, MD, PhD; Joost H.W. Rutten, MD, PhD; Maarten J.G. Leening, MD, MSc; Rozemarijn Vliegenthart, MD, PhD; Germaine C. Verwoert, MSc; Gabriel P. Krestin, MD, PhD; Matthijs Oudkerk, MD, PhD; Moniek P.M. de Maat, PhD; Frank W.G. Leebeek, PhD; Francesco U.S. Mattace-Raso, MD, PhD; Jan Lindemans, PhD; Albert Hofman, MD, PhD; Ewout W. Steyerberg, PhD; Aad van der Lugt, MD, PhD; Anton H. van den Meiracker, MD, PhD; and Jacqueline C.M. Witteman, PhD

Optimizing coronary heart disease risk prediction can help target preventive interventions. This study examined whether the addition of newer markers (N-terminal fragment of prohormone B-type natriuretic peptide [NT-proBNP], von Willebrand factor antigen, fibrinogen, chronic kidney disease, leukocyte count, C-reactive protein, homocysteine, uric acid, coronary artery calcium [CAC] score, carotid intima–media thickness, peripheral artery disease, and pulse wave velocity) to the Framingham risk score improved prediction in 5933 asymptomatic patients. Only CAC score and possibly NT-proBNP resulted in clinically meaningful improvements. Despite these favorable results for CAC score, it is expensive and exposes individuals to radiation, so its use for coronary risk assessment requires further evaluation.

Topics: coronary heart disease risk, netherlands
  
Suetonia C. Palmer, MB ChB, PhD; Lucia Di Micco, MD; Mona Razavian, MB BS; Jonathan C. Craig, MB ChB, DCh, MM, PhD; Vlado Perkovic, MB BS, PhD; Fabio Pellegrini, MSc; Massimiliano Copetti, MSc, PhD; Giusi Graziano, MSc; Gianni Tognoni, MD; Meg Jardine, MB BS, PhD; Angela Webster, MB BS, PhD; Antonio Nicolucci, MD; Sophia Zoungas, MD, PhD; and Giovanni F.M. Strippoli, MD, PhD, MPH, MM

Antiplatelet agents are given for cardiovascular prevention to patients with chronic kidney disease (CKD). This review found that glycoprotein IIb/IIIa inhibitors or clopidogrel increased major bleeding but had little or no effect on myocardial infarction, death, or coronary revascularization in patients with CKD who had acute coronary syndromes or were undergoing percutaneous coronary revascularization. In other patients with CKD who had or were at risk for cardiovascular disease, antiplatelet regimens increased minor bleeding, reduced myocardial infarction, and had uncertain effects on mortality. However, evidence was weak in quality and derived primarily from subgroup analysis of trials.

Topics: antiplatelet agents, hemorrhage, kidney failure, chronic, cardiovascular system, mortality, myocardial infarction, cardiovascular ...
  

A recently engineered H5N1 virus that is transmissible between ferrets may also be transmissible between humans. If the virus were to escape the laboratory, it could endanger the lives of hundreds of millions of persons. The author of this commentary discusses why the possible benefits of this research do not justify taking such risk and how the principle of free and open exchange of scientific information has come into a rare moment of conflict with that of “first, do no harm.”

Topics: influenza, maryland, infection, viruses, case fatality rate, influenza a virus, h5n1 subtype, ...
  

The controversy surrounding the newly engineered H5N1 influenza virus escalated when the National Science Advisory Board for Biosecurity recommended that the work be published but recommended significant voluntary redactions. The author of this commentary discusses the polarizing responses to this action and the research and believes that the knowledge gained by these and future experiments under appropriate safeguards is likely to allow critical understanding of influenza transmission and virulence.

Topics: influenza, orthomyxoviridae
  

Dapagliflozin offers a novel, insulin-independent mechanism of action for diabetes treatment. In this issue, Wilding and colleagues report on the effectiveness and safety of adding dapagliflozin to insulin therapy or insulin therapy with other oral hyperglycemic agents. The editorialist discusses the findings, as well as the U.S. Food and Drug Administration deliberation regarding approval of dapagliflozin.

Topics: glucose, sodium, dapagliflozin
  

In this issue, Kavousi and colleagues assessed 12 novel risk markers for coronary heart disease. The CAC score added the most to the Framingham risk score, and NT-proBNP level was a close second. The editorialist discusses the study and urges that strong evidence is needed before these new risk markers are incorporated into routine clinical practice.

Topics: pharmacotherapy, statins, intima media thickness, diabetes mellitus, myocardial infarction, computed tomography, cardiovascular ...
  
Andreas Thyssen, BS

I debated whether what I was about to ask would be laughed off or viewed as another naive question from a medical student along for his first ambulance ride. I decided to risk it and turned back toward the paramedic. “How do you deliver a baby when your legs are handcuffed to the bed?”

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Sondra S. Crosby, MD

Stepping off the plane in an unfamiliar country, jet-lagged, and unable to speak a word of the native language, I was a little disoriented. I met my patient at the hotel in less than an hour of my arrival. I could tell he was apprehensive. This unique and complicated situation demanded creative and unorthodox measures.

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Paul S. Agutter, MD, PhD; and P. Colm Malone, MD
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Amir Qaseem, MD, PhD, MHA; Roger Chou, MD; Linda Humphrey, MD, MPH; and Paul Shekelle, MD, PhD
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Jan D. Raguse, MD; Christian Camerer, MD; Frank Bergmann, MD; Christiane Schewe, MD; and Dirk Schürmann, MD
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Risa Denenberg, NP, MSN
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Topics: pharmaceutical adjuvants, tamoxifen, breast cancer
  
Topics: hiv, antitubercular agents, mortality, anti-retroviral agents
  
Topics: warfarin
  
Topics: simvastatin
  
Topics: statins, cerebral hemisphere hemorrhage
  
Topics: chronic obstructive airway disease, fracture, inhaled corticosteroid
  
Topics: chest x-ray, mortality, lung cancer, elderly
  
Topics: acute cerebrovascular accidents, hyperglycemia, fever, deglutition
  
Topics: obesity, behavior therapy
  
Topics: obesity, weight reduction, counseling, life style
  
Topics: acetaminophen, ibuprofen, knee pain
  
Topics: antibiotics, mortality, nosocomial pneumonia
  
Topics: diabetes mellitus, type 2, insulin, dapagliflozin
  
Topics: veterans, glucose control, african american, financial incentives
  
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